Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Celecoxib in Treating Patients With Head and Neck Cancer That Can Be Removed By Surgery

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Biomarker/Laboratory analysis, Treatment Active 18 and over Other CHUV-CEPO-161-05 EU-20627, NCT00357617

Objectives

Primary

1. Evaluate the changes in molecular markers of angiogenesis before and after treatment with celecoxib in tumor tissues of patients with resectable head and neck squamous cell carcinoma.

Secondary

1. Evaluate the changes in molecular markers of angiogenesis before and after treatment with celecoxib in blood tissues of these patients.
2. Evaluate the effects of celecoxib on indirect measures of tumor perfusion, as measured by perfusion CT scan, in these patients.
3. Evaluate the effects of celecoxib on apoptosis and proliferation rate on tumor cells and on endothelial cells in these patients.
4. Identify potential new markers of the activity of cyclooxygenase-2 inhibitors and identify new pathways of potential interests by performing gene expression profiling of tumor tissues before and after exposure to celecoxib.

Entry Criteria

Disease Characteristics:

• Histologically confirmed or high clinical suspicion of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
  • No carcinoma of sinonasal or nasopharynx



• Clinical stage T1-4, N0-2, M0 disease
  • Tumor must be considered resectable with planned surgical excision
  • No lymph nodes > 6 cm (N3)
  • No distant metastasis

Prior/Concurrent Therapy:

• More than 2 months since prior and no other concurrent anticancer or investigational drugs
• More than 2 weeks since prior and no other concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids
• No prior radiotherapy to the head and neck region
• No concurrent radiotherapy
• No concurrent therapeutic anticoagulation
• No concurrent administration of any of the following:
  • Other cyclooxygenase-2 inhibitors
  • Aspirin
    • Low-dose aspirin for cardiovascular prophylaxis allowed
  • Aluminum and magnesium-containing antacids
  • ACE inhibitors
  • Furosemide
  • Known inhibitors of P450 2C9 (e.g., fluconazole, fluoxetine, fluvoxamin, isoniazid, omeprazole)
  • Known inducers of P450 2C9 (e.g., rifampin)
  • Lithium
  • Acenocoumarol

Patient Characteristics:

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10 g/dL
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Creatinine clearance ≥ 60 mL/min
• AST and ALT ≤ 2.5 times ULN
• Bilirubin normal
• History of prior malignancy allowed if there is no evidence of recurrence or metastases at the time of screening
• No comorbidity that precludes operability
• No known liver impairment
• Known recent gastric or duodenal ulcer allowed if treated for > 6 weeks prior to study enrollment
• No known hypersensitivity to celecoxib
• No known allergic reactions to sulfonamides, aspirin, or other NSAIDs
• No psychological, familial, sociological, or geographical condition that would interfere with study compliance and follow-up schedule
• Not pregnant or nursing
• Negative pregnancy test

Expected Enrollment

A total of 24 patients will be accrued for this study.

Outcomes

Molecular markers of angiogenesis in tumor tissues (PGE2, VEGF, MMP-9, sFlt-1, ERK phosphorylation, PKB phosphorylation, and ErbB2 levels)

Molecular markers in plasma (VEGF, MMP-9, and sFlt1)
Molecular marker in urine (PGE2)
Apoptosis/proliferation in tumor cells and endothelial cells
Gene expression profiling in fresh tumor tissues (Erb-B2, c-IAP-2, PAI-1, MAPK-4, integrin α V, N-CAM, caspase 6, ErbB2 transducer, angiopoietin like-2, interleukin-8, and MMP13)
Tumor perfusion imaging by perfusion CT scan

Outline

This is an open-label, nonrandomized, uncontrolled study.

Patients undergo panendoscopy and tumor biopsy on day 0. Patients receive oral celecoxib twice daily beginning on day 1 and continuing for at least 14 days*. Patients then undergo definitive surgery.

 [Note: *Treatment continues until the day before surgery.]

Tumor, blood, and urine samples are collected at baseline and periodically during study. Tumor quantification by perfusion CT scan is performed at baseline and after treatment with celecoxib. Biological markers are detected by immunohistochemistry and enzyme immunoassay. Blood vascular density, apoptosis, proliferation, and endothelial cell:tumor ratio are measured by indirect hemagglutination. Gene expression is measured by microarray analysis.

After surgery, patients are followed at 4 weeks and then periodically thereafter.

Trial Contact Information

Trial Lead Organizations

Centre Hospitalier Universitaire Vaudois

Francois Luthi, MD, Protocol chair		Ph: 41-213-140-155

Switzerland
	Lausanne
	Centre Hospitalier Universitaire Vaudois
		Francois Luthi, MD	Ph:  41-213-140-155

Registry Information
Official Title		Evaluation of the Effect of Celecoxib on Angiogenesis Markers in Patients with Operable Head and Neck Squamous Cell Carcinoma
Trial Start Date		2006-06-15
Registered in ClinicalTrials.gov		NCT00357617
Date Submitted to PDQ		2006-06-06
Information Last Verified		2008-01-29